The proposed work is aimed at understanding the mechanisms of endogenous hypertriglyceridemia in man. During the next year, our efforts will focus on two areas. One series of investigations will aim at attempts to define the mechanism of dietary-induced hypertriglyceridemia in nonobese young rats. We have been able to consistently produce hypertriglyceridemia by feeding a sucrose-lard diet to these animals. The hypertriglyceridemia bears striking resemblance to the characteristics of endogenous hypertriglyceridemia in man, i.e., rats are hypertriglyceridemic, hyperinsulinemic, and secrete increased amounts of very low density (VLDL)-triglyceride (TG). We have established the fact that the liver is the site of the increased VLDL-TG secretion, and next year we plan to measure the concentration of several hepatic enzymes and substrates which might be responsible for the increase in hepatic VLDL-TG secretion. Our second major focus will be an attempt to define the role of changes in lipoprotein lipase (LPL) activity in the age-related increased incidence of hypertriglyceridemia. We have extablished that plasma TG levels rise with age, and it appears that this is due to a defect in VLDL-TG removal from plasma. Since the enzyme LPL is thought to play a major role in control of VLDL-TG uptake, we plan to investigate the effects of age on LPL activity. Preliminary experiments have already established the fact that there is a defect insofar as adipost tissue LPL will demonstrate a 4-5 fold response to food ingestion in young rats. In old rats, this food-induced rise in LPL activity is lost. In the next year we plan to carry out experiments attempting to define the mechanisms responsible for this loss in the ability of LPL activity to be normally responsive to food as a function of age.